Bimetallic Cu@Ru Core-Shell Structures with Ligand Effects for Endo-Exogenous Stimulation-Mediated Dynamic Oncotherapy.

Dynamic therapies, which induce reactive oxygen species (ROS) production in situ through endogenous and exogenous stimulation, are emerging as attractive options for tumor treatment. However, the complexity of the tumor substantially limits the efficacy of individual stimulus-triggered dynamic therapy. Herein, bimetallic copper and ruthenium (Cu@Ru) core-shell nanoparticles are applied for endo-exogenous stimulation-triggered dynamic therapy. The electronic structure of Cu@Ru is regulated through the ligand effects to improve the adsorption level for small molecules, such as water and oxygen. The core-shell heterojunction interface can rapidly separate electron-hole pairs generated by ultrasound and light stimulation, which initiate reactions with adsorbed small molecules, thus enhancing ROS generation. This synergistically complements tumor treatment together with ROS from endogenous stimulation. In vitro and in vivo experiments demonstrate that Cu@Ru nanoparticles can induce tumor cell apoptosis and ferroptosis through generated ROS. This study provides a new paradigm for endo-exogenous stimulation-based synergistic tumor treatment.

Glucose oxidase and ruthenium nanorods-embedded self-healing polyvinyl alcohol/polyethylene imine hydrogel for simultaneous photothermal/photodynamic/starvation therapy and skin reconstruction.

Tumor recurrence and wound healing represent significant burdens for tumor patients after the surgical removal of melanomas. Wound dressings with wound healing and anticancer therapeutic abilities could help to solve these issues. Thus, a hybrid hydrogel made of polyvinyl alcohol (PVA) and polyethylene imine (PEI) was prepared by cross-linking imine bond and boronic acid bond. This hydrogel was loaded with ruthenium nanorods (Ru NRs) and glucose oxidase (GOx) and named as nanocomposite hydrogel (Ru/GOx@Hydrogel), exhibiting remarkable photothermal/photodynamic/starvation antitumor therapy and wound repair abilities. Ru NRs are bifunctional phototherapeutic agents that simultaneously exhibit intrinsic photothermal and photodynamic functions. Three-dimensional composite hydrogel loaded with GOx can also consume glucose in the presence of O2 during tumor starvation therapy. Near-infrared (NIR) light-triggered hyperthermia can not only promote the consumption of glucose, but also facilitate the ablation of residual cancer cells. The antitumor effect of the Ru/GOx@Hydrogel resulted in significant improvements, compared to those observed with either phototherapy or starvation therapy alone. Additionally, the postoperative wound was substantially healed after treatment with Ru/GOx@Hydrogel and NIR irradiation. Therefore, the Ru/GOx@Hydrogel can be used as a multi-stimulus-responsive nanoplatform that could facilitate on-demand controlled drug release, and be used as a promising postoperative adjuvant in combination therapy.

"Spark" PtMnIr Nanozymes for Electrodynamic-Boosted Multienzymatic Tumor Immunotherapy.

Multienzyme-mimicking redox nanozymes capable of efficient reactive oxygen species (ROS) generation and cellular homeostasis disruption are highly pursued for cancer therapy. However, it still faces challenges from the complicate tumor microenvironment (TME) and high chance for tumor metastasis. Herein, well-dispersed PtMnIr nanozymes are designed with multiple enzymatic activities, including catalase (CAT), oxidase (OXD), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPx), which continuously produce ROS and deplete glutathione (GSH) concurrently in an "inner catalytic loop" way. With the help of electrodynamic stimulus, highly active "spark" species (Ir3+ and Mn3+) are significantly increased, resulting in an effective cascade enzymatic and electrodynamic therapy. Moreover, the cyclic generation of ROS can also facilitate ferroptosis and apoptosis in tumor cells, boosting synergistic therapy. Importantly, lung metastasis inhibition is found, which confirms efficient immunotherapy by the combined effect of immunogenic cell death (ICD) and Mn2+-induced cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (cGAS-STING) pathway, contributing great potential in the treatment of malignant tumors.

Palladium nanoparticle based smart hydrogels for NIR light-triggered photothermal/photodynamic therapy and drug release with wound healing capability.

Tumor recurrence and wound repair are two major challenges following cancer surgical resection that can be addressed through precision nanomedicine. Herein, palladium nanoparticles (Pd NPs) with photothermal and photodynamic therapy (PTT/PDT) capacity were successfully synthesized. The Pd NPs were loaded with chemotherapeutic doxorubicin (DOX) to form hydrogels (Pd/DOX@hydrogel) as a smart anti-tumor platform. The hydrogels were composed of clinically approved agarose and chitosan, with excellent biocompatibility and wound healing ability. Pd/DOX@hydrogel can be used for both PTT and PDT with a synergistic effect to kill tumor cells. Additionally, the photothermal effect of Pd/DOX@hydrogel allowed the photo-triggered drug release of DOX. Therefore, Pd/DOX@hydrogel can be used for near-infrared (NIR)-triggered PTT and PDT as well as for photo-induced chemotherapy, efficiently inhibiting tumor growth. Furthermore, Pd/DOX@hydrogel can be used as a temporary biomimetic skin to block the invasion of foreign harmful substances, promote angiogenesis, and accelerate wound repair and new skin formation. Thus, the as-prepared smart Pd/DOX@hydrogel is expected to provide a feasible therapeutic solution following tumor resection.

Biodistribution, degradability and clearance of 2D materials for their biomedical applications.

Two-dimensional (2D) materials have evolved to be a class of rapidly advancing chemical entities in the biomedical field. Nevertheless, potential side effects and safety concerns severely limit their clinical translation. After administration, 2D materials cross multiple biological barriers and are distributed throughout the body. Only the portion that accumulates at the diseased sites exerts a therapeutic effect, whereas those distributed elsewhere may cause damage to healthy tissues and interference to normal physiological function of various organs. To achieve maximum therapeutic efficacy and minimum adverse effects simultaneously, the delivery of 2D materials must be targeted at diseased sites to reach therapeutic concentrations, and the materials must possess sufficient degradation and clearance rates to avoid long-term toxicity. Therefore, it is essential to understand the biodistribution and destiny of 2D materials in vivo. In this review, first, we provide a comprehensive picture of the strategies that are currently adopted for regulating the in vivo fate of 2D materials, including modulations of their size, surface properties, composition, and external stimuli. Second, we systematically review the biodistribution, degradation, and metabolism of several newly emerged 2D materials. Finally, we also discuss the development opportunities of 2D materials in the biomedical field and the challenges to be addressed.

Photocatalytic Microbial Fuel Cells and Performance Applications: A Review.

In recent years, photocatalytic microbial fuel cells have gradually become a hot research topic in pollutant treatment, using either in situ or indirectly the oxidation of organic pollutants by catalytic materials under light and the biodegradation and mineralization of various components in wastewater by microorganisms, or through the generation of electricity by the microbial fuel cell (MFC) system to promote the photogeneration and separation of electrons and holes by the catalytic materials of the photocatalytic cell (PC) system. This study aims to provide new ideas for the development of environmentally friendly wastewater treatment technologies by investigating the use of photocatalytic cells for the efficient degradation and resource utilization of target pollutants. This study aims to raise awareness of the use of photocatalytic microbial fuel cells for pollutant degradation by providing an overview of the practical status of photocatalytic microbial fuel cells. This is achieved by reviewing the key cathode development, production capacity, and progress in the degradation of pollutants in photocatalytic microbial fuel cells. The issues facing future developments are also discussed in terms of how photocatalytic microbial fuel cells work and how they degrade pollutants. This study shows that photocatalytic microbial fuel cells are beneficial for achieving renewable energy (bioenergy, photovoltaic, etc.) capacity and dealing with environmental pollution and that this is a novel technology that deserves to be promoted to achieve the current dual carbon targets.

Recent Development of MOF-Based Photothermal Agent for Tumor Ablation.

Metal-organic frameworks (MOFs) are 3D-architecture compounds of metal ions and organic molecules with sufficient and permanent porosity, showing great potential as a versatile platform to load various functional moieties to endow the hybrid materials with specific applications. Currently, a variety of photothermal nanometals have been embedded into organic ligands for integrating the unique photothermal effects with the merits of MOFs to improve their performances for cancer therapy. In this review, we have summarized a series of novel MOF-based photothermal materials for this unique therapeutic modality against tumors from three main aspects according to their chemical compositions and structures, i) metal-doped MOF, ii) organic-doped MOF, and iii) polymer-coated MOF. In addition, we have summarized the latest developments and characteristics of MOF-based photothermal agents, such as good biocompatibility, low toxicity, and responsive photothermal conversion without destroying the structure of hybrid photothermal agent. At last, we addressed the future perspectives of MOF-based photothermal agent in the field of phototherapy.

Progress and prospects of reversible solid oxide fuel cell materials.

Reversible solid oxide fuel cell (RSOFC) is an energy device that flexibly interchanges between electrical and chemical energy according to people's life and production needs. The development of cell materials affects the stability and cost of the cell, but also restricts its market-oriented development. After decades of research by scientists, a lot of achievements and progress have been made on RSOFC materials. According to the composition and requirements of each component of RSOFC, this article summarizes the research progress based on materials and discusses the merits and demerits of current cell materials in electrochemical performance. According to the efficiency of different materials in solid oxide fuel cell (SOFC mode) and solid oxide electrolyzer (SOEC mode), the challenges encountered by RSOFC in the operation are evaluated, and the future development of RSOFC materials is boldly prospected.

A Near-Infrared Light Triggered Composite Nanoplatform for Synergetic Therapy and Multimodal Tumor Imaging.

Transition-metal chalcogenide compounds with facile preparation and multifunctional elements act as ideal photothermal agents for cancer theranostics. This work synthesizes Cu7.2S4/5MoS2 composite nanoflowers and investigates the crystal growth mechanism to optimize the synthesis strategy and obtain excellent photothermal therapy agents. Cu7.2S4/5MoS2 exhibits a high photothermal conversion efficiency of 58.7% and acts as a theranostic nanoplatform and demonstrated an effective photothermal-chemodynamic-photodynamic synergetic therapeutic effect in both in vitro and in vivo tests. Moreover, Cu7.2S4/5MoS2 shows strong photoacoustic signal amplitudes and computed tomographic contrast enhancement in vivo. These results suggest a potential application of Cu7.2S4/5MoS2 composite nanoflowers as photo/H2O2-responsive therapeutic agents against tumors.

Enhanced Photocatalytic Degradation of Methylene Blue by WO3 Nanoparticles Under NIR Light Irradiation.

Photocatalysts have been paid great attention owing to their excellent performance in the degradation of dangerous organic pollutants. Herein, a novel longitudinally grown WO3 photocatalyst was prepared by using a hydrothermal process, which had strong ultraviolet, visible light absorption, and weak near-infrared (NIR) absorption. The WO3 photocatalyst exhibited excellent performance in the rapid degradation of methylene blue (MB) in industry. The photothermal effect is mainly responsible for the rapid degradation of MB under NIR laser irradiation. Besides, different morphologies and structures affect the degradation of MB. The longitudinally grown enlarged the contact area between photocatalyst and MB, and expanded the scope of the absorption wavelength of light, enhancing the stability of photocatalytic materials. So this unique transverse longitudinal structure exhibited a potential capability for degrading organic pollutants.

Photothermal Effect: The Amygdaloidal Nano-Structure Based on Bi2S3 for the Enhanced Degradation of Rhodamine B Under Irradiation by NIR.

In recent years the photothermal effect, an auxiliary strategy for increasing the degradation rate of pollutants under irradiation by near-infrared (NIR), has become a research focus. In this study a novel amygdaloidal nanophotocatalyst, Bi2S3, was synthesized by a traditional approach using a hydrothermal process, in which Bi2S3 nanostructures were spread out like a peacock's tail. The produced Bi2S3 photocatalyst exhibited excellent performance in the rapid degradation of Rhodamine B (RB). This proved that the photothermal effect is mainly responsible for the rapid degradation of RB under NIR laser irradiation. Moreover, it was found that the photothermal effect could not degrade the products with NIR radiation in darkness. However, with the support of visible radiation, the photothermal effect of the Bi2S3 photocatalyst enhanced degradation of RB (degradation rate 90% under 1 h). This novel structure exhibited a potential ability for degrading pollution in industry or agriculture.

An upconversion nanoplatform with extracellular pH-driven tumor-targeting ability for improved photodynamic therapy.

Upconversion nanoparticles (UCNPs) are widely utilized for photodynamic therapy (PDT) due to their specific upconverting luminescence that utilizes near infrared (NIR) light to excite photosensitizers (PSs) for PDT. The efficiency of UCNP-based PDT will be improved if the cancer-targeting property of nanomedicine is enhanced. Herein, we employed the pH low insertion peptide (pHLIP), a cancer-targeting moiety, to functionalize an 808 nm excited UCNP-based nanoplatform that has a minimized over-heating effect to perform PDT. pHLIP can bring cargo specifically into cancer cells under an acidic environment, realizing the effective active-targeting abilities to cancer cells or tumor due to acidosis. The pHLIP-functionalized nanoplatform was assembled and well characterized. The nanoplatform shows an efficient NIR-irradiated PDT effect in cancer cells, especially under a slightly acidic condition that mimics the tumor microenvironment, and this effectiveness is attributed to the targeting properties of pHLIP to cancer cells under acidic conditions that favor the entry of the nanoplatform. Furthermore, the pHLIP-functionalized nanoplatform shows a favorable safety profile in mice with a high maximum tolerated dose (MTD), which may broaden the availability of administration in vivo. The efficient in vivo antitumor activity is achieved through intratumor injection of the nanoplatform followed by NIR irradiation on the breast tumor. The nanoparticles are largely accumulated in the tumor site, revealing the excellent tumor-targeting properties of the pHLIP-functionalized nanoplatform, which ensures efficient PDT in vivo. Moreover, the nanoparticles have a long retention time in the bloodstream, indicating their stability in vivo. Overall, we provide an example of a UCNP-based nanosystem with tumor-targeting properties to perform efficient PDT both in vitro and in vivo.

Upconversion in Nanostructured Materials: From Optical Tuning to Biomedical Applications.

Photon upconversion that is characterized by high-energy photon emission followed by lower-energy excitation has been conventionally studied in bulk materials for several decades. This unique nonlinear luminescence process has become a subject of great attention since 2000 when upconverted emission was demonstrated in nanostructured crystals. In comparison with their bulk counterparts, nanostructured materials provide more room for optical fine-tuning by allowing flexible compositional integration and structural engineering. Moreover, the high colloidal stability of nanoparticles coupled with high amenability to surface functionalization opens up a number of new applications for upconversion, especially in the fields of biology and life science. In this focus review, we discuss recent developments in upconversion materials through nanostructural design and review emerging biomedical applications that involve these nanostructured upconversion materials. We also attempt to highlight challenging problems of these nanomaterials that constrain further progress in utilizing upconversion processes.

A General Strategy for Ligand Exchange on Upconversion Nanoparticles.

Lanthanide-doped upconversion nanoparticles with a suitable surface coating are appealing for biomedical applications. Because high-quality upconversion nanoparticles are typically prepared in an organic solvent and passivated by hydrophobic oleate ligands, a convenient and reliable method for the surface modification of upconversion nanoparticles is thus highly desired to satisfy downstream biological investigations. In this work, we describe a facile and versatile strategy for displacing native oleate ligands on upconversion nanoparticles with a diversity of hydrophilic molecules. The ligand-exchange procedure involves the removal of original oleate ligands followed by the attachment of new ligands in a separate step. The successful coating of relevant ligands was confirmed by Fourier transform infrared spectroscopy, thermogravimetry analysis, and ζ-potential measurement. The surface-modified nanoparticles display high stability and good biocompatibility, as revealed by electron microscopy, photoluminescence spectroscopy, and cytotoxicity assessment. Our study demonstrates that functional biomolecules such as biotin can be directly immobilized on the nanoparticle surface using this approach for the quick and effective detection of streptavidin.

An upconversion nanoplatform for simultaneous photodynamic therapy and Pt chemotherapy to combat cisplatin resistance.

Platinum-based antineoplastic drugs are among the first-line chemotherapeutic agents against a variety of solid tumors, but toxic side-effects and drug resistance issues limit their clinical optimization. Novel strategies and platforms to conquer cisplatin resistance are highly desired. Herein, we assembled a multimodal nanoplatform utilizing 808 nm-excited and biocompatible core-shell-shell upconversion nanoparticles (UCNPs) [NaGdF4:Yb/Nd@NaGdF4:Yb/Er@NaGdF4] that were covalently loaded with not only photosensitizers (PSs), but also Pt(iv) prodrugs, which were rose bengal (RB) and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2NH2)2], respectively. The UCNPs had the capability to convert near infrared (NIR) light to visible light, which was further utilized by RB to generate singlet oxygen. At the same time, the nanoplatform delivered the Pt(iv) prodrug into cancer cells. Thus, this upconversion nanoplatform was able to carry out combined and simultaneous photodynamic therapy (PDT) and Pt chemotherapy. The nanoplatform was well characterized and the energy transfer efficiency was confirmed. Compared with free cisplatin or UCNPs loaded with RB only, our nanoplatform showed significantly improved cytotoxicity upon 808 nm irradiation in both cisplatin-sensitive and -resistant human ovarian cancer cells. A mechanistic study showed that the nanoparticles efficiently delivered the Pt(iv) prodrug into cancer cells, resulting in Pt-DNA damage, and that the nanoplatform generated cellular singlet oxygen to kill cancer cells. We, therefore, provide a comprehensive strategy to use UCNPs for combined Pt chemotherapy and PDT against cisplatin resistance, and our nanoplatform can also be used as a theranostic tool due to its NIR bioimaging capacity.

Graphitic Carbon Nanocubes Derived from ZIF-8 for Photothermal Therapy.

Graphitic carbon nanocubes (GCNCs) were prepared by pyrolysis of ZIF-8 nanocubes. The GCNCs resemble the structure of N-doped graphite and exhibit a high photothermal conversion efficiency of 40.4%. In vitro tests demonstrate that the GCNCs are highly biocompatible and induce an effective photothermal therapy effect under 808 nm irradiation. Our study provides a facile strategy for preparing functional carbon nanomaterials of prescribed size, morphology, and porous structure for bioapplications.

Intracellular Delivery: Diamond-Nanoneedle-Array-Facilitated Intracellular Delivery and the Potential Influence on Cell Physiology (Adv. Healthcare Mater. 10/2016).

G. Zhu, W. Zhang, X. Chen, and co-workers show on page 1157 that diamond needle arrays can efficiently deliver biomolecules into living cells. The study paves the way to a wide application of the nanonneedle treatment by systematically investigating the influence of the treatment on metabolic signal pathways.

Multimodal Upconversion Nanoplatform with a Mitochondria-Targeted Property for Improved Photodynamic Therapy of Cancer Cells.

Upconversion nanoparticles (UCNPs) with the capacity to emit high-energy visible or UV light under low-energy near-infrared excitation have been extensively explored for biomedical applications including imaging and photodynamic therapy (PDT) against cancer. Enhanced cellular uptake and controlled subcellular localization of a UCNP-based PDT system are desired to broaden the biomedical applications of the system and to increase its PDT effect. Herein, we build a multimodal nanoplatform with enhanced therapeutic efficiency based on 808 nm excited NaYbF4:Nd@NaGdF4:Yb/Er@NaGdF4 core-shell-shell nanoparticles that have a minimized overheating effect. The photosensitizer pyropheophorbide a (Ppa) is loaded onto the nanoparticles capped with biocompatible polymers, and the nanoplatform is functionalized with transcriptional activator peptides as targeting moieties. Significantly increased cellular uptake of the nanoparticles and dramatically elevated photocytotoxicity are achieved. Remarkably, colocalization of Ppa with mitochondria, a crucial subcellular organelle as a target of PDT, is proven and quantified. The subsequent damage to mitochondria caused by this colocalization is also confirmed to be significant. Our work provides a comprehensively improved UCNP-based nanoplatform that maintains great biocompatibility but shows higher photocytotoxicity under irradiation and superior imaging capabilities, which increases the biomedical values of UCNPs as both nanoprobes and carriers of photosensitizers toward mitochondria for PDT.

Diamond-Nanoneedle-Array-Facilitated Intracellular Delivery and the Potential Influence on Cell Physiology.

Vertical arrays of nanostructures can provide access to the cell cytoplasma and probe intracellular molecules. Here, the simple combination of diamond nanoneedle arrays with centrifugation-induced supergravity is shown to efficiently deliver drugs and biomaterials into the cytosol within several minutes, negotiating the endocytososomal system. The potential influence of the technique on cell metabolism is thoroughly studied. By detecting the phosphorylated histone variant H2AX (pH2AX) in the nucleus, it is proved that the operating process will not lead to DNA double-strand breaks. However, the mechanical disruption can temporarily improve the permeability of the cell membranes. Nanoneedle treatment affects cell metabolism at multiple points. The treatment can slightly elevate the apoptotic signal in A549 cells and can significantly increase the production of reactive oxygen species (ROS) in cells, particularly if combined with anticancer drugs. Meanwhile, the activity of cytosolic glucose 6-phosphate dehydrogenase (G6PD) is also raised to counterbalance the elevated ROS content. A detected depolarization of the mitochondrial membrane potential suggests mitochondrial involvement in the intracellular redox reactions and cell apoptosis which are induced by diamond nanoneedle treatment. Overall this study provides a novel understanding on the intracellular delivery mediated by nanoneedles, especially the impact on cell physiology.

A core-shell-shell nanoplatform upconverting near-infrared light at 808 nm for luminescence imaging and photodynamic therapy of cancer.

Upconversion nanoparticles (UCNPs) have been extensively explored for photodynamic therapy (PDT) and imaging due to their representative large anti-Stokes shifts, deep penetration into biological tissues, narrow emission bands, and high spatial-temporal resolution. Conventional UCNP-based PDT system, however, utilizes exitation at 980 nm, at which water has significant absorption, leading to a huge concern that the cell killing effect is from the irradiation due to overheating effect. Here we report an efficient nanoplatform using 808-nm excited NaYbF4:Nd@NaGdF4:Yb/Er@NaGdF4 core-shell-shell nanoparticles loaded with Chlorin e6 and folic acid for simultaneous imaging and PDT. At this wavelength, the absorption of water is minimized. High energy transfer efficiency is achieved to generate cytotoxic singlet oxygen. Our nanoplatform effectively kills cancer cells in concentration-, time-, and receptor-dependent manners. More importantly, our nanoplatform is still able to efficiently generate singlet oxygen beneath 15-mm thickness of muscle tissue but 980 nm excitation cannot, showing that a higher penetration depth is achieved by our system. These results imply that our nanoplatform has the ability to effectively kill intrinsic tumor or the center of large tumors through PDT, which significantly improves the anticancer efficacy using UCNP-based PDT system and broadens the types of tumors that could be cured.